From Imperial College London (A.C.G., F.A.-B.), Imperial College Healthcare NHS Trust, St. Mary's Hospital (A.C.G.), Intensive Care National Audit and Research Centre (P.R.M., K.M.R.), University College London Hospital (R.H.), King's College London (M.S.-H.), and Guy's and St. Thomas' NHS Foundation Trust (M.S.-H.), London, University of Oxford (A. Beane) and NHS Blood and Transplant (L.J.E.), Oxford, and University of Bristol, Bristol (C.A.B.) - all in the United Kingdom; Monash University (A.D.N., A. Buzgau, A.C.C., A.M.H., S.P.M., J.C.P., C.G., S.A.W.) and Alfred Health (A.D.N., A.C.C.), Melbourne, VIC, Fiona Stanley Hospital (E. Litton, K.O.) and University of Western Australia (E. Litton), Perth, WA, University of Sydney and Royal Prince Alfred Hospital, Sydney (A.E.P.), and St. John of God Hospital, Subiaco, WA (S.A.W.) - all in Australia; University College Dublin, Dublin (A.D.N.); King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (Y.M.A.); Hospital Raymond Poincaré (Assistance Publique-Hôpitaux de Paris) and Université Paris Saclay-Université de Versailles Saint-Quentin-en-Yvelines-INSERM, Garches, and Université de Versailles Saint-Quentin-en-Yvelines-Université Paris Saclay, Montigny-le-Bretonneux - all in France (D.A.); University Medical Center Utrecht, Utrecht (W.B.-P., M.J.M.B., H.L.L., E.R., L.P.G.D.), and Radboudumc, Nijmegen (F.L.V.) - both in the Netherlands; Berry Consultants, Austin, TX (L.R.B., M.A.D., M.F., E. Lorenzi, A.M., C.T.S., R.J.L., S.B.); St. Michael's Hospital Unity Health (Z.B., J.C.M., M.S.S.) and University Health Network and University of Toronto (P.R.L.), Toronto, Université de Sherbrooke, Sherbrooke, QC (F.L.), University of British Columbia, Vancouver (S.M.), University of Alberta, Edmonton (W.I.S.), Université Laval, Québec City (A.F.T.), and University of Manitoba, Winnipeg, MB (R.Z.) - all in Canada; Jena University Hospital, Jena, Germany (F.M.B.); Auckland City Hospital (E.J.D., T.E.H., S.P.M., R.L.P., C.J.M.), Middlemore Hospital (S.C.M.), and University of Auckland (R.L.P.), Auckland, and Medical Research Institute of New Zealand, Wellington (T.E.H., S.P.M., A.M.T.) - all in New Zealand; University of Antwerp, Wilrijk, Belgium (H.G.); University of Oxford, Bangkok, Thailand (R.H.); National Intensive Care Surveillance, Colombo, Sri Lanka (R.H.); UPMC Children's Hospital of Pittsburgh (C.M.H.) and University of Pittsburgh (K.M.L., F.B.M., B.J.M., S.K.M., C.W.S., D.C.A.), Pittsburgh; Queen's University Belfast and Royal Victoria Hospital, Belfast, Northern Ireland (D.F.M.); University of Helsinki and Helsinki University Hospital, Helsinki (V.P.); and Harbor-UCLA Medical Center, Torrance, CA (R.J.L.).
N Engl J Med. 2021 Apr 22;384(16):1491-1502. doi: 10.1056/NEJMoa2100433. Epub 2021 Feb 25.
BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).
背景：白细胞介素-6 受体拮抗剂在 2019 年冠状病毒病（COVID-19）危重症患者中的疗效尚不清楚。
方法：我们在一项正在进行的国际、多因素、适应性平台试验中评估了托珠单抗和沙利鲁单抗。COVID-19 患者在 ICU 中开始器官支持后 24 小时内，随机分配接受托珠单抗（8mg/kg 体重）、沙利鲁单抗（400mg）或标准治疗（对照组）。主要结局是呼吸和心血管器官支持无天数，将住院死亡（赋值为-1）和无器官支持天数联合到第 21 天的一个有序量表上。该试验采用贝叶斯统计模型，具有优越性、疗效、等效性或无效性的预设标准。比值大于 1表示生存率提高、无器官支持天数增加或两者兼有。
结果：托珠单抗和沙利鲁单抗均符合疗效的预设标准。当时，353 例患者被分配至托珠单抗组，48 例患者被分配至沙利鲁单抗组，402 例患者被分配至对照组。托珠单抗组无器官支持天数的中位数为 10 天（四分位距，-1 至 16），沙利鲁单抗组为 11 天（四分位距，0 至 16），对照组为 0 天（四分位距，-1 至 15）。调整后的累积优势比为托珠单抗组 1.64（95%可信区间，1.25 至 2.14），沙利鲁单抗组 1.76（95%可信区间，1.17 至 2.91），与对照组相比，均具有超过 99.9%的优势后验概率和 99.5%的优势后验概率。90 天生存率分析显示，联合使用白细胞介素-6 受体拮抗剂可改善生存率，与对照组相比，风险比为 1.61（95%可信区间，1.25 至 2.08），优势后验概率超过 99.9%。所有次要分析均支持这些白细胞介素-6 受体拮抗剂的疗效。
结论：在 ICU 接受器官支持的 COVID-19 危重症患者中，白细胞介素-6 受体拮抗剂托珠单抗和沙利鲁单抗的治疗改善了结局，包括生存率。（REMAP-CAP 临床试验.gov 编号，NCT02735707.）
N Engl J Med. 2021-4-22
N Engl J Med. 2023-12-21
N Engl J Med. 2021-4-22
Cochrane Database Syst Rev. 2021-3-18
N Engl J Med. 2021-8-26
Microorganisms. 2025-7-31
Infect Drug Resist. 2025-8-8
Circ Genom Precis Med. 2025-8
Front Cell Infect Microbiol. 2025-7-7
J Assoc Med Microbiol Infect Dis Can. 2025-6-27
JAMA Netw Open. 2025-7-1
N Engl J Med. 2021-4-22
N Engl J Med. 2021-1-7
Nature. 2021-3
N Engl J Med. 2020-12-3
N Engl J Med. 2020-10-21
EClinicalMedicine. 2020-10
Zotero 插件
